HER2-Positive Breast Cancer

Last week, the FDA announced that it would grant priority review to pertuzumab (Perjeta), as a neoadjuvant treatment for women with HER2-positive early-stage breast cancer.

A 6-month regimen of treatment with trastuzumab for HER2-positive breast cancer failed to show noninferiority with the standard 12-month treatment regimen after 3.5 years of follow-up in the open-label, randomized, phase III PHARE trial.

The addition of everolimus (Novartis) to combination trastuzumab/vinorelbine leads to a significant improvement in progression-free survival compared with placebo in advanced and metastatic HER2-positive breast cancer.

A high baseline level of soluble human epidermal growth factor receptor 2 (sHER2) was a prognostic indicator of shorter disease-free survival among patients with early-stage HER2-positive breast cancer, according to results from the North Central Cancer Treatment Group adjuvant trial N9831.

In the HERA trial, benefit for invasive lobular breast cancer patients with 1 year of trastuzumab maintenance was similar to invasive ductal carcinoma patients.

A study confirmed that PIK3CA mutations negatively affect survival in patients with HER2-positive breast cancer treated with the anti-HER2 therapy trastuzumab.

A new study shows that drugs targeting HER2 might provide good results in the rare non-small-cell lung cancer (NSCLC) patients with HER2 mutations.

Researchers participating in the phase III EMILIA trial have identified tumor biomarkers that can identify patients that are more likely to benefit from T-DM1. In the trial, women whose tumors had higher HER2 expression were most likely to benefit from the therapy.

This article reviews clinical data informing the effective management of HER2-positive metastatic breast cancer, including the optimal sequence of HER2-targeted agents.

As more drugs become available in the HER2 arena, clinicians will be faced with increasing challenges regarding which sequences and combinations of drugs will be the best for their patients. In the era in which we practice, a great deal of this is likely to be dictated by the payers.

Third, how much do we really know about de novo and acquired resistance to trastuzumab and lapatinib? There are several possible clinical relevant mechanisms of trastuzumab resistance, including crosstalk with other receptors, amplification of the PI3K/AKT pathway, alteration of the trastuzumab binding domain, and loss of HER2 expression.

Last month brought the accelerated approval by the US Food and Drug Administration (FDA) of a fourth agent targeting the human epidermal growth factor receptor 2 (HER2) oncogene product: TDM-1 (Kadcyla), a conjugate of trastuzumab and a cytotoxic, emtansine.

A new study from cancer stem cell experts at the University of Michigan is challenging the notion that trastuzumab (Herceptin) only works for HER2-positive breast cancer.

Ado-trastuzumab emtansine, formerly known as T-DM1, improved progression-free survival as first-line treatment for patients with HER2-positive metastatic breast cancer, when compared with the standard treatment of trastuzumab plus docetaxel in a randomized phase II multicenter study.

The FDA has approved ado-trastuzumab emtansine (Kadcyla), known as T-DM1 in development, for the treatment of women with metastatic HER2-positive breast cancer.

Such a systematic review of the current status of mTOR inhibitors in the treatment of breast cancer demonstrates holes in our knowledge of the role of the tumor, the host, and metabolic factors in breast cancer progression.

Efforts to identify clinical biomarkers of response or resistance to mTOR inhibitors are ongoing. This review will summarize results of preclinical and clinical studies as well as ongoing clinical trials with mTOR or dual PI3K/mTOR inhibitors.

I see a time in the not too distant future when we’ll define tumors this way. What will our subspecialties be? Rather than a breast clinic or a lung clinic, will we perhaps be attending a “HER2 clinic” or an “mTOR clinic” instead?

This second article in our two-part series on targeted therapies in solid tumors covers the emergence of targeted therapies for the treatment of two common malignancies: lung cancer and breast cancer.

A new drug combination of lapatinib (Tykerb) and capecitabine (Xeloda) shrunk brain tumors in HER2-positive breast cancer patients whose cancer had spread to the brain, showing it is active as a first-line brain metastases treatment with similar efficacy to whole-brain radiotherapy.

According to a study of 12,500 women treated for invasive breast cancer, treatment with trastuzumab (Herceptin) increases the risk of congestive heart failure and cardiomyopathy.

Results of a phase III trial show early, promising data that the subcutaneous formulation of trastuzumab (Herceptin) is as efficacious and safe as the intravenous version of the drug.

The diagnosis of central nervous system (CNS) recurrence is a much dreaded outcome among breast cancer patients, and its incidence varies with disease stage and cancer subtype.

Pertuzumab has been approved in combination with trastuzumab (Herceptin) and docetaxel chemotherapy for women whose breast cancer overexpress the HER2 receptor and who have not received prior systemic treatment.

Women previously treated for HER2-positive breast cancer have lower rates of relapse when given a novel peptide vaccine. The AE37 vaccine showed a 43% risk reduction in these patients after 22 months of follow-up in a phase IIb clinical trial.

Women with metastatic HER2-positive breast cancer treated with a taxane-based chemotherapy in combination with trastuzumab as a first-line of treatment have a longer progression-free survival compared to chemotherapy in combination with lapatinib (Tykerb)

A 13-gene signature can predict the development of brain metastasis among patients with advanced HER2-positive breast cancer who have estrogen-receptor (ER)-negative tumors. The results were presented at a breast cancer session at the 2012 meeting of the American Society of Clinical Oncology.

Results of a large phase III trial shows that a new oncology therapy, trastuzumab emtansine (T-DM1), significantly delays progression of disease in women with HER2-positive advanced breast cancer previously treated with a taxane chemotherapy and trastuzumab (Herceptin).

It may not be appropriate, nor always considered standard, to recommend neoadjuvant chemotherapy for all patients for whom adjuvant therapy was recommended before surgery. Indeed, tumor size and nodal status play a role, as do hormone receptors, in determining the appropriate extent of adjuvant therapy.

Treatment of HER2-positive cancers has improved rapidly over the past decade, and the pace of progress continues to accelerate. The advances have been fueled in part by the conduct of neoadjuvant studies, which have aided in the development of novel therapies and more effective combination regimens.